Development of Hollow Microspheres as Floating Controlled-Release Systems for Cardiovascular Drugs: Preparation and Release Characteristics

Hollow microspheres of cellulose acetate loaded with four cardiovascular drugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffusion-evaporation method. The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%. The microspheres had smooth surfaces, with free-flowing and good-packing properties. Scanning electron microscopy (SEM) confirmed their hollow structures, with sizes in the range 489–350 μm. The microspheres tended to float over the gastric media for more than 12 h. The drug loaded in hollow microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for more than 8 h. The release kinetics followed different transport mechanisms depending on the nature of the drug molecules.     

中空层状羟基磷灰石微球对溶菌酶的吸附与缓释研究

利用锂钙硼玻璃在磷酸盐溶液中的原位转化反应制备表面多孔且具有中空层状结构的羟基磷灰石(HA)微球,以溶菌酶为蛋白的药物模型,研究了中空层状结构的羟基磷灰石微球对溶菌酶的吸附及缓释特性,结果显示,中空微球对不同浓度的溶菌酶溶液,具有不同的吸附机理,当溶菌酶溶液的浓度低于0.8mg/mL时,溶菌酶的吸附主要发生在微球的外表面,符合Langmuir模型,释放速率较快,48h内基本释放完全;当溶菌酶溶液的浓度高于0.8mg/mL时,溶菌酶扩散进入微球内部及球壁的微孔中,使得吸附量显著增加,满足Henry吸附模型,溶菌酶的释放周期明显增加,可持续释放800h,微球对蛋白具有很好的缓释效果。     

Captopril floating and/or bioadhesive tablets: design and release kinetics

Two viscosity grades of hydroxypropylmethylcellulose (HPMC 4000 and 15000 cps) and Carbopol 934P were used to prepare captopril floating tablets. In vitro dissolution was carried out in simulated gastric fluid (enzyme free) at 37°C ± 0.1°C using the USP apparatus 2 basket method. Compared to conventional tablets, release of captopril from these floating tablets was apparently prolonged; as a result, a 24-hr controlled-release dosage form for captopril was achieved. Drug release best fit both the Higuchi model and the Korsmeyer and Peppas equation, followed by first-order kinetics. While tablet hardness and stirring rate had no or little effect on the release kinetics, tablets hardness was found to be a determining factor with regard to the buoyancy of the tablets.     

空心玻璃微球表面接枝聚苯乙烯及其性能研究

空心玻璃微球表面改性有利于改善其与基体间的相容性,提高复合泡沫性能.通过接枝聚苯乙烯对空心玻璃微球进行表面处理,采用SEM、IR、热失重等方法分析了反应条件对接枝的影响.结果表明,接枝反应过程中提高反应温度、延长反应时间有利于接枝率的提高,但温度过高会加速单体自聚,降低接枝率.接枝处理后,随着聚合物层的增厚,空心玻璃微球表面缺陷减小,破损率降低,抗压强度得到一定程度提高.     

PTF敏化TiO_2中空微球的制备及可见光催化性能

分别以聚甲基丙烯酸甲酯(PMMA)微球和9-苯基-2,3,7-三羟基-6-荧光酮(PTF)为模板和敏化剂,将水热法与浸渍法相结合,合成了一种新颖的染料敏化TiO2中空微球(PTF-h-TiO2)。通过SEM、FT-IR、XRD、UV-Vis DRS等技术对样品的结构形貌进行表征。以亚甲基蓝(MB)、氯霉素(CAP)为模型反应,分别考察了水热时间、水热温度、模板添加量和煅烧温度对h-TiO2光催化性能的影响,并评价了h-TiO2和PTFh-TiO2的紫外-可见光催化活性。结果表明,当模板添加量为5%(质量分数),水热时间6 h,水热温度120℃及煅烧温度500℃时,h-TiO2具有优异的紫外-可见光催化活性,由此制得的PTF-h-TiO2微球具有良好的可见光催化活性。在氙灯(150 W,400 nm)照射下,PTF-h-TiO2催化降解10 mg/L MB溶液,50 min,其降解率可达98.1%;降解20 mg/L CAP,120 min,其降解率达86.9%。     

Development and evaluation of hollow mesoporous silica microspheres bearing on enhanced oral delivery of curcumin

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.     

TiO2-ZnO复合中空微球的制备及光催化性能

以Ti（SO₄）₂和Zn（NO₃）₂为原料,采用水热法制备TiO₂-ZnO复合中空微球光催化剂。通过FTIR、XRD、SEM、紫外可见漫反射光谱（UV-Vis DRS）、XPS及N₂吸附-脱附等方法对TiO₂-ZnO复合光催化剂的结构和性能进行表征,并以亚甲基蓝（MB）为目标降解物,评价TiO₂-ZnO复合中空微球光催化活性。结果表明,TiO₂-ZnO光催化剂具有中空微球结构,粒径为1~2 μm,比表面积为30.46 m2/g。TiO₂的加入可提高ZnO对光的吸收,有效降低电子空穴复合率。在高压Hg灯照射下,TiO₂-ZnO复合中空微球的光催化性能均高于纯ZnO,其中Zn（NO₃）₂与Ti（SO₄）₂摩尔比为1:0.7条件下制备的TiO₂-ZnO复合中空微球样品表现出较好的光催化活性,光照60 min,对MB的降解率可达95.8%,其光催化降解速率是纯ZnO的4.3倍。      

纳米结构氧化镁空心球壳的制备及吸附镍离子性能研究

以Pickering乳液的液滴为模板制备纳米结构MgO空心球壳,用SEM、XRD、BET等对空心球壳进行了表征,探讨了其形成机理,并考察了纳米结构MgO空心球壳对水中Ni2+的吸附性能。结果表明,MgO空心球壳为方镁石结构,比表面积为28m2/g;其平均粒径为63μm,表面由平均宽度为65nm的纳米片层构成。Pickering乳液油水界面的部分MgO通过水化反应转变成Mg(OH)2,复合在未反应的MgO粒子上,形成MgO/Mg(OH)2空心球壳;MgO/Mg(OH)2空心球壳经焙烧后得到纳米结构MgO空心球壳。当纳米结构MgO空心球壳用量为0.4g/L时,溶液(初始浓度25mg/L)中Ni2+的去除率为98.3%。     

热处理温度对镀钴空心微球镀层晶体结构及电磁性能的影响

对采用化学镀方法制得的镀Co空心玻璃微球进行了不同温度的热处理,对其在不同温度热处理下的表面形貌、晶型、电磁参数与吸波性能以及磁性能进行了研究。研究结果发现,随着热处理温度升高,镀层先后出现微区熔融直至较严重的熔融和镀层剥落现象;镀层Co发生由HCP到FCC的晶型转变且转变程度提高。热处理温度对镀Co微球介电常数影响比较显著,对磁导率影响则比较小;在2~18GHz频段,经过800和1000℃热处理的镀Co空心玻璃微球介电常数大幅提高,而磁导率变化不大,电磁波反射率显著降低。镀Co空心玻璃微球矫顽力随热处理温度上升而下降,热处理后镀Co微球磁滞损耗略有下降。可以预测经过800和1000℃热处理的镀Co微球吸波性能会有较大的提高。     

Development and in vitro evaluation of floating rosiglitazone maleate microspheres

Background: Various approaches have been used to retain the dosage form in stomach as a way of increasing the gastric residence time, including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extensible, or swellable systems; and superporous hydrogel systems. Aim?: The objective of this study was to prepare and evaluate floating microspheres of rosiglitazone maleate for the prolongation of gastric residence time. Method: The microspheres were prepared by solvent diffusion–evaporation method using ethyl cellulose and hydroxypropylmethylcellulose. A full factorial design was applied to optimize the formulation. Results: Preliminary studies revealed that the polymer:drug ratio, concentration of polymer, and stirring speed significantly affected the characteristics of microspheres. The optimum batch exhibited a prolonged drug release, remained buoyant for >12 hours, high entrapment efficiency, and particle size in the order of 350 μm. Conclusion: The results of 32 full factorial design revealed that the concentration of ethylcellulose 7 cps (X₁) and stirring speed (X₂) significantly affected drug entrapment efficiency, percentage release after 8 h and particle size of microspheres.     

Cellulose acetate microspheres as floating depot systems to increase gastric retention of antidiabetic drug: formulation, characterization and in vitro-in vivo evaluation

Gastric emptying is a complex process that is highly variable and makes the in vivo performance of drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug delivery systems for more than 12 hours utilizing floating or hydrodynamically controlled drug delivery systems. The objective of this investigation was to develop a floating, depot-forming drug delivery system for an antidiabetic drug based on microparticulate technology to maintain constant plasma drug concentrations over a prolonged period of time for effective control of blood sugar levels. Formulations were optimized using cellulose acetate as the polymer and evaluated in vitro for physicochemical characteristics and drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in healthy male albino mice. The shape and the surface morphology of the prepared microspheres were characterized by optical microscopy and scanning electron microscopy. In vitro drug release studies were performed and drug release kinetics were calculated using the linear regression method. Effects of stirring rate during preparation and polymer concentration on the size of microspheres and drug release were observed. The prepared microspheres exhibited prolonged drug release (more than 10 hours) and remained buoyant for over 10 hours. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 73% to 98% were obtained. The release rate decreased and the mean particle size increased at higher polymer concentrations. Stirring speed affected the morphology of the microspheres. This investigation revealed that upon administration, the biocompatible depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain orally given drug. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.     

SiO2中空微球改性含硅芳炔树脂及其复合材料的结构与性能

采用SiO₂中空微球对含硅芳炔树脂（PSAC）进行改性,制备了SiO₂/PSAC复合材料,以改善PSAC固化后质脆的缺点,提高PSAC基复合材料的力学性能,拓展PSAC在航空航天领域的应用。对SiO₂/PSAC复合材料和石英纤维布增强SiO₂/PSAC（QF-SiO₂/PSAC）复合材料的结构与性能进行了研究,采用SEM分析SiO₂/PSAC树脂浇铸体和QF-SiO₂/PSAC复合材料断面微观结构,并分析SiO₂的增韧机制。采用DMA和TGA分析了SiO₂/PSAC复合材料耐热性能和热稳定性,虽然SiO₂会导致树脂耐热性能略有下降,但其中空结构使树脂具有优异介电性能。当SiO₂的添加量达2wt%时,SiO₂/PSAC树脂浇铸体弯曲强度达22.3 MPa,失重5%温度为551℃,1 000℃残留率为86.5%;QF-2SiO₂/PSAC复合材料的弯曲强度为298.3 MPa,弯曲模量达31.0 GPa,分别提高了27.5%、59.0%;当SiO₂添加量为5wt%时,QF-5SiO₂/PSAC复合材料的剪切强度提高了16.0%。      

空心玻璃微珠表面磁控溅射镀铝及其对人工介质材料介电性能的影响

采用直流磁控溅射法在空心玻璃微珠表面镀Al膜,利用XRD和SEM研究了镀Al 微珠的相结构和形貌。将镀Al微珠、未镀Al微珠与高分子粘合剂混合制得人工介质材料,利用网络分析仪测定其在8.2~12.4 GHz频率范围的介电性能。结果表明,采用磁控溅射方法可在玻璃微珠表面包覆金属Al膜,Al膜与基体的结合力较好。在镀铝微珠加入量相同的情况下,玻璃微珠表面铝膜越厚,则人工介质材料的介电常数越大。在Al膜厚度相同的情况下,镀Al微珠加入量越多,则人工介质材料的介电常数越大。所制备的人工介质材料介电损耗小于30.02,密度小于0.8g/cm。     

壳聚糖微球的制备及其在药物载体中的应用

壳聚糖因其具有良好的生物学特性而成为药物载体研究的热点。药物经壳聚糖负载后,不仅能够达到缓释控释的目的,还能够改变药物的给药方式,降低药物不良反应,提高药物生物利用度。本文就壳聚糖微球的制备及其在药物载体中的应用作一综述。     

Preparation and characteristics of erythromycin microspheres for lung targeting

Background: If erythromycin is micronized into microspheres with suitable particle size, it can improve pulmonary drug concentration to maximize its effectiveness and minimize the adverse side effects. Aim: In this study, erythromycin gelatin microspheres (EM-GMS) were prepared and some characteristics of EM‐GMS were investigated. The drug-targeting index (DTI) of EM-GMS was evaluated to predict their potential as a targeted delivery system. Method: Erythromycin was microencapsulated with gelatin by a double emulsion solvent evaporation method. Some characteristics of EM-GMS, including morphology, particle size, in vitro release, and safety were researched. Results: EM-GMS had a spherical shape and smooth surface morphology. The drug loading and encapsulation efficiency of EM-GMS were 13.56 ± 0.25% and 55.82 ± 2.23%, respectively. The release of erythromycin from EM-GMS showed an initial burst and following a sustained release, with an accumulate release of 80% at 4 hours. The EM-GMS was safe since there was no vein irritation and no hemolysis on the erythrocyte of rabbit at 3.5 mg/mL and a LD50 of 173.07 mg/kg. After administering EM-GMS to rabbits, the concentration of erythromycin in lung was 15.92 times higher than that in plasma and the DTI of EM-GMS in lung was 6.65 as compared with erythromycin lactobionate. Conclusions: The preparation technology of EM-GMS for lung targeting was successful and the quality of microspheres was good.     

Gd_2O_3空心微球的制备及Gd_2O_3/丁基橡胶复合材料低频阻尼性能

以分散聚合法制备的聚苯乙烯(PS)微球作为模板,通过均相沉淀法制备前驱体PS-Gd(OH)CO_3复合微球,高温煅烧后得到Gd_2O_3空心微球,将其与丁基橡胶复合制备低频高阻尼Gd_2O_3/丁基橡胶复合材料。采用FTIR、SEM、TEM分析、TG分析仪、XRD分析和XPS对Gd_2O_3空心微球的形貌与结构组成进行表征。将Gd_2O_3空心微球与粉体分别作为填料加入丁基橡胶中制备Gd_2O_3/丁基橡胶复合材料。结果表明:Gd_2O_3空心微球由立方萤石结构的颗粒组成,外空心直径为0.9μm,壳层厚度约为100nm;添加空心微球的复合材料阻尼性能较好;与纯丁基橡胶相比,Gd_2O_3/丁基橡胶复合材料的低频阻尼性能明显提高。     

Formulation and in vitro evaluation of prolonged release floating microspheres of atenolol using multicompartment dissolution apparatus

The aim of the present work was to prepare floating microspheres of atenolol as prolonged release multiparticulate system and evaluate it using novel multi-compartment dissolution apparatus. Atenolol loaded floating microspheres were prepared by emulsion solvent evaporation method using 3² full factorial design. Formulations F1 to F9 were prepared using two independent variables (polymer ratio and % polyvinyl alcohol) and evaluated for dependent variables (particle size, percentage drug entrapment efficiency and percentage buoyancy). The formulation(F8) with particle size of 329?±?2.69 µm, percentage entrapment efficiency of 61.33% and percentage buoyancy of 96.33% for 12?h was the of optimized formulation (F8). The results of factorial design revealed that the independent variables significantly affected the particle size, percentage drug entrapment efficiency and percentage buoyancy of the microspheres. In vitro drug release study revealed zero order release from F8 (98.33% in 12?h). SEM revealed the hollow cavity and smooth surface of the hollow microspheres.     

Uniform lanthanide-doped Y2O3 hollow microspheres: Controlled synthesis and luminescence properties

Lanthanide-doped uniform pure cubic phase Y₂O₃ hollow microspheres have been successfully synthesized via a facile, high yield urea-based coprecipitation route with assistant of carbon spheres templates. The diameter and shell thickness of the microspheres can be manipulated by adjusting carbon sphere templates. Under a 980 nm excitation, Yb³⁺/Er³⁺, Er³⁺, Yb³⁺/Tm³⁺-doped Y₂O₃ hollow microspheres emit bright upconversion red, green, blue light with high purity, respectively, while Eu³⁺, Eu³⁺/Tb³⁺-doped Y₂O₃ hollow microspheres exhibit intense downconversion red light under the excitation of 254 nm ultraviolet light. Especially, the 610 nm emission intensity of Eu³⁺ in the Eu³⁺/Tb³⁺-codoped Y₂O₃ hollow microspheres is almost 5 times of that in the Y₂O₃:Eu³⁺ hollow microspheres indicating the occurring of the energy transfer from Tb³⁺ to Eu³⁺ ions.     

Spray-drying as a method for microparticulate controlled release systems preparation: advantages and limits. I. Water-soluble drugs

Spray-drying was used for the preparation of paracetamol/eudragit RS or RL or ethylcellulose microspheres to verify the possibility of their use in controlled-release solid-dosage forms formulation and try to determine advantages and limits of the technique of such use. Microspheres were first characterized by scanning electron microscopy, differential scanning calorimetry, x-ray diffractometry, and in vitro dissolution studies and then used for the preparation of tablets. During this step, the compressibility of the spray-dried powders was also evaluated. In vitro dissolution studies were performed also on the tablets and their release control was accessed. Although powders were unable to slow down drug release, tablets obtained from microsphere compression showed a good capability of controlling paracetamol release when eudragit RS or ethylcellulose was used, even at low polymer amounts.     

Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release

Hollow hydroxyapatite (HA) microspheres were fabricated by a simple spray drying method in this study. Moreover, the dissolution behavior of these hollow HA microspheres after immersion in simulated body fluid (SBF) was also studied. The results indicated that the dissolution of the HA microspheres in SBF is not homogeneous in a layer-by-layer fashion but was preferential at different locations of the particle surface. Generically, dissolution preferentially occurs on the location with looser structure and high porosity of the microspheres. The degradable HA microspheres are expected to have potential applications in bone local drug delivery systems.